International Journal of Pediatric Otorhinolaryngology, 17 (1989) 305-311 Elsevier PEDOT 00587 305 Laryngotracheal involvement bullosa * 3 * * in epidermolysis Carlos Gonzalez ’ and Rudolf Roth ’ ’ Otolaryngology Head and Neck Surgery Service and ’ Dermatology Service, Walter Reed Army Medical Center, Washington, D. C. 20307 (U.S.A.) (Received 20 September 1988) (Revised version received 13 November 1988) (Accepted 5 March 1989) Key words: Epidermolysis bulIosa; Larynx; Trachea Abstract Epidermolysis bullosa (EB) is a rare hereditary skin disease of infancy that can involve the mucous membranes of the oral cavity. Laryngotracheal involvement is rare. The disease is characterized by bullae formation in response to minor trauma. There are at least 18 described types of EB, however, there are 3 basic categories. These are simplex (with disruption above the basement membrane), dystrophic (in which disruption is below the basement membrane), and junctional (in which the split is within the lamina lucida). The prognosis of the different types ranges from early death usually secondary to overwhelming sepsis, to long term survivals with lack of growth retardation or significant dystrophic scarring. Presently, survival appears to be the only reliable criteria for distinguishing the benign and lethal forms of EB. Airway obstruction secondary to laryngotracheal involvement should be considered in any child with epidermolysis bullosa presented with symptoms of respiratory distress. Because there are few predictive prognostic indicators in the neonatal period, tracheotomy should be considered early in an effort to prevent further laryngeal injury from intubation, in those patients that will survive. * Presented at the Annual Meeting of the American Society of Pediatric Otolaryngology, Kiawah Island, S.C., April 20-23, 1988. * * The opinions and assertions contained herein are those of the authors and are not to be construed as official or as reflecting the views of the Department of Defense, Department of the Army or the Uniformed Services University of the Health Sciences. Correspondence: C. Gonzalez, Walter Reed Army Medical Center, Otolaryngology Head and Neck Surgery Service, Washington D.C. 20307, U.S.A. 0165-5876/89/$03.50 0 1989 Elsevier Science Publishers B.V.
Transcript
International Journal of Pediatric Otorhinolaryngology, 17 (1989) 305-311
Elsevier
PEDOT 00587
305
Laryngotracheal involvement bullosa * 3 * *
in epidermolysis
Carlos Gonzalez ’ and Rudolf Roth ’
’ Otolaryngology Head and Neck Surgery Service and ’ Dermatology Service,
Walter Reed Army Medical Center, Washington, D. C. 20307 (U.S.A.)
(Received 20 September 1988)
(Revised version received 13 November 1988)
(Accepted 5 March 1989)
Key words: Epidermolysis bulIosa; Larynx; Trachea
Abstract
Epidermolysis bullosa (EB) is a rare hereditary skin disease of infancy that can involve the mucous membranes of the oral cavity. Laryngotracheal involvement is rare. The disease is characterized by bullae formation in response to minor trauma. There are at least 18 described types of EB, however, there are 3 basic categories. These are simplex (with disruption above the basement membrane), dystrophic (in which disruption is below the basement membrane), and junctional (in which the split is within the lamina lucida). The prognosis of the different types ranges from early death usually secondary to overwhelming sepsis, to long term survivals with lack of growth retardation or significant dystrophic scarring. Presently, survival appears to be the only reliable criteria for distinguishing the benign and lethal forms of EB. Airway obstruction secondary to laryngotracheal involvement should be considered in any child with epidermolysis bullosa presented with symptoms of respiratory distress. Because there are few predictive prognostic indicators in the neonatal period, tracheotomy should be considered early in an effort to prevent further laryngeal injury from intubation, in those patients that will survive.
* Presented at the Annual Meeting of the American Society of Pediatric Otolaryngology, Kiawah
Island, S.C., April 20-23, 1988.
* * The opinions and assertions contained herein are those of the authors and are not to be construed as
official or as reflecting the views of the Department of Defense, Department of the Army or the
Uniformed Services University of the Health Sciences.
Correspondence: C. Gonzalez, Walter Reed Army Medical Center, Otolaryngology Head and Neck Surgery Service, Washington D.C. 20307, U.S.A.
Epidermolysis bullosa is a rare hereditary skin disease of infancy that can involve the mucous membranes of the oral cavity. The disease is characterized by bullae formation in response to minor trauma. Histologically, EB can be divided into 3 categories: (a) simplex, where blister cleavage occurs within the epidermis and healing occurs without scarring, (b) junctional, where blister cleavage occurs below the epidermis but above the basal lamina healing with mild atrophic changes, and (c) dystrophic, where blister cleavage occurs below the basal lamina and healing results in dystrophic changes [2]. Laryngotracheal involvement is rare. We report a two-month-old infant with junctional epidermolysis bullosa (JEB) that developed inspiratory stridor progressing to respiratory failure. Endoscopic examination re- vealed laryngo-tracheal bullae formation. Tracheotomy was performed, however, the child died of overwhelming sepsis on the 5th postoperative day.
Case presentation
NS was a 2948 gram male product of a 37 week gestation, born via normal spontaneous vaginal delivery. At delivery, the patient was found to have bullous lesions of the right ear, nares, and the periumbilical and perianal areas. Initial viral culture and Tzanck smear were reported positive for herpes simplex, and the patient was readmitted to the hospital on the 7th day of life for intravenous acyclovir therapy. At readmission, new lesions were found over the lower extremities, and the patient was noted to have dystrophic nails (Fig. 1). Further workup, including viral and bacterial cultures of blister fluid, blood, CSF, eye, and nasopharynx, as well as Tzanck smears and direct immunofluorescence studies of blister fluid for herpes simplex were negative. TORCH titers were notable for a HSV titer of 1 : 8. Bunch
Fig. 1. Dystrophic fingernails with bullous involvement of the dorsal aspects of the hand.
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Fig. ? I. Endoscopic appearance of epiglottis demonstrating bullous lesion on the lingual su Irface.
biopsies of two lesions revealed a subepidermal bulla with focal epidermal necrosis, and the absence of any reticular or balloon degeneration (Fig. 2). Di rect im- munoflu orescence of both lesional and non-lesional skin was negative. Indirect
Fig. 4. Tracheal involvement with epidermolysis bullosa 1 cm above carina.
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immunofluorescence of serum was also negative. Transmission electron microscopy revealed a bulla within the lamina lucida. Immunomapping revealed bullous pemphigoid antigen (present in the lamina lucida, but attached to the basal cell layer) on the roof of the bulla and KF-1 antigen (present in the basal lamina) on the floor. These studies are consistent with a diagnosis of junctional epidermolysis bullosa.
On the 29th day of life, the patient was noted to develop a hoarse cry with inspiratory stridor. Oral mucosa and tongue bullous lesions were noted. Symptoms of airway compromise initially improved, however, within two days the child developed significant stridor with evidence of respiratory failure. The child under- went direct laryngoscopy and bronchoscopy which revealed bullous lesions of the epiglottis (Fig. 3), glottis (posterior commissure) and cervical trachea (Fig. 4). Tracheotomy was performed without complication. Postoperatively the child devel- oped sepsis which was unresponsive to maximal medical support. On April 30, 1987 the patient died.
Discussion
Junctional epidermolysis bullosa (JEB) refers to a group of mechanobullous disorders characterized by blister formation at sites of relatively minor trauma. Since the clinical manifestations were first described by Herlitz in 1935, at least 7 clinical types of JEB have been described. The prognosis of’ the different types ranges from early death usually secondary to overwhelming sepsis, to long-term survivals with lack of growth retardation or significant dystrophic scarring. Pre- sently, survival appears to be the only reliable criteria for distinguishing the benign and lethal forms of JEB.
Epidermolysis bullosa has been subdivided into 3 major groups, based on both clinical findings and on the histologic level of blister formation [2,11]. Epidermolytic (simplex) EB is characterized by non-dystrophic lesions and a level of split within the epidermis. Junctional EB is associated with primarily atrophic changes and cleavage between the basal layer of cells and the basal lamina, or in the lamina lucida. Finally, dermolytic (dystrophic) EB is characterized by primarily dystrophic changes and a blister cleavage below the basal lamina. Within each of these major groups, several specific clinical types have been described. At least 7 clinical subtypes of junctional EB (JEB) have been identified.
Our patient, with blister formation within the lamina lucida identified by both electron microscopy and immunomapping, had a severe form of JEB. All subtypes of JEB are inherited in an autosomal recessive manner, and show lesions that heal without scarring but with time develop atrophy. Although blistering does not occur in utero, prenatal diagnosis is possible by fetoscopic skin biopsy. Blistering and erosions are present at or shortly after birth, and may, after a few days, become generalized.
The most severe subset of JEB, EB letalis or junctional EB of Herlitz, shows numerous blisters with dystrophic teeth and nails, and often results in death due to
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sepsis within a few months. These patients may show involvement of the oral mucosa, and hoarseness may indicate laryngeal involvement. Other patients have been reported to have involvement in the trachea and bronchioles. The widespread degree of skin and oral involvement in our patient, as well as his rapid demise, would put him in this category.
Bullous involvement of the mucous membranes of the oral cavity and esophagus is recognized with JEB. Laryngotracheal involvement, however, is rare. Most re- ported cases of laryngeal or tracheal involvement have been in patients with the more benign and chronic form of epidermolysis bullosa [l-lo]. Thompson, et al. [lo] in 1980 reported acute airway compromise in a 3-week-old infant with epider- molysis bullosa dystrophica. Tracheotomy was performed, and the patient was eventually decannulated. Earlier reports have lacked information on the type of EB, however, recent reports of laryngeal involvement have been reported in children with JEB [2,4,7,8]. Outcome has ranged from hoarseness with no need for tracheot- omy [8], to tracheotomy [7], to death (present case). The case we present developed rapid onset of respiratory failure in the first month of life. Endoscopic examination revealed glottic and tracheal involvement. Tracheotomy was performed to avoid the possibility of further glottic injury, secondary to endotracheal intubation. Ulti- mately the child succumbed to generalized sepsis. The etiology of airway obstruction in these children is unclear. Most reports have noted blisters as well as ruptured vesicles with granulation and ulceration. Glossop et al. [4] noted cystic swelling of the seromucinous glands in the supraglottic larynx as the cause of airway obstruc- tion. In those patients that survive, cicatricial bands and webs ultimately develop
[I,7,8,91. Airway obstruction secondary to laryngotracheal involvement should be consid-
ered in any child with epidermolysis bullosa presenting with symptoms of respira- tory distress. Because there are few predictive prognostic indicators in the neonatal period, tracheotomy should be considered early, in an effort to prevent further laryngeal injury from intubation, in those patients that will survive.
References
1 Cohen, S.R., Landing, B.H. and Isaacs, H., Epidermolysis bullosa associated with laryngeal stenosis,
Ann. Otol. Rhinol. Laryngol., 87 Suppl. 52 (1978) 25-28.
2 Cooper, T.W. and Bauer, E.A., Epidermolysis bullosa: a review, Ped. Dermatol., 1 (1984) 181-188.
3 Davies, H. and Atherton, D.J., Acute laryngeal obstruction in junctional epidermolysis bullosa, Ped.
Dermatol., 4 (1987) 988101. 4 Glossop, L.P., Michaels, L. and Bailey, C.M., Epidermolysis bullosa letalis causing acute respiratory
failure: a’case presentation and review of the literature, Int. J. Pediatr. Otorhinolaryngol., 7 (1984)
281-288. 5 Gonzalez, A., Schachner, L. and Miller, M., Junctional epidermolysis of the larynx (letter), Pediatrics,
